Intragastric administration of dahuang zhechong pill modulates TGF-β1/smad signaling pathway in murine model of experimental silicosis

Abstract

Objectives: Since DHZCP had significant inhibitory effects on liver and kidney fibrosis, we hypothesize that DHZCP could also inhibit pulmonary fibrosis. Therefore, the aim of this study is to examine the effect of DHZCP on silicosis, a type of pulmonary fibrosis caused by silica dust, and its underlying mechanism. Methods: Pulmonary fibrosis was induced by inhalation of silica (SiO2) dust in mice which were then randomly divided into 5 groups: pulmonary fibrosis model group, high-dose DHZCP group, medium-dose DHZCP group, low-dose DHZCP group and Tetrandrine group. The normal control group mice were not exposed to SiO2 dust. After 28 days of continuous intragastric administration of DHZCP, the mice were sacrificed. The histopathology of lungs, the levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and hydroxyproline (HYP) in serum. Besides, the expression of transforming growth factor‑β1 (TGF-β1), α-smooth muscle actin (α-SMA), Smad2, Smad3 and Smad7 in lung tissue were examined. Results: The mice with silicosis was generated with an observed inflamed lung tissues and elevated inflammatory cytokines. DHZCP significantly reduced serum levels of TNF-α, IL-6, IL-1β and HYP in mice with lung fibrosis. DHZCP treatment remarkably downregulated mRNA and protein levels of TGF-β1, α-SMA, Smad2 and Smad3 in lung tissue, while increased the protein level of Smad7. Conclusions: These results demonstrated that DHZCP could alleviate pulmonary fibrosis induced by SiO2. The anti-fibrotic effects of DHZCP are conferred by decreasing inflammation and pulmonary fibrosis, which may be related to the TGF-β1/Smad pathway.

Keywords

• Silica
• Dahuangzhechong pill
• Inflammation
• Pulmonary fibrosis
• TGF-β1/Smad pathway